Disease-free survival (DFS) [ Time Frame: Time from randomization to recurrence, development of second primary cancer, or death from any cause, assessed up to 10 years ] [ Designated as safety issue: No ]

A weighted mixture of the log hazard rates was used to estimate the effective (increased) hazard rate on the experimental arm. Using this adjusted alternative hazard rate, the target is instead a reduction in the hazard rate of 20% for DFS events when comparing each experimental arm to placebo.

LVEF decline defined as LVEF below the institutional lower limit of normal, where the drop is at least 16% from baseline.

DFS among patients with clear cell histology [ Time Frame: Up to 13 years ] [ Designated as safety issue: No ]

The sequentially rejective method will be used for this analysis.

Differences in fatigue assessed by FACIT Fatigue Subscale [ Time Frame: Baseline to up to 22 weeks ] [ Designated as safety issue: No ]

For each of the two instruments, descriptive statistics at each timepoint, including Cronbach's alpha, will be provided. Repeated measures analyses will be used to examine the treatment and time effects on scores. Spearman's correlation coefficient will be used to explore associations between scores on the FACIT Fatigue subscale and scores on the PROMIS Fatigue-SF1.

Frequency of clinically significant congestive heart failure (CHF) grade 3 or higher using the Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Baseline to up to 8 weeks after final treatment ] [ Designated as safety issue: Yes ]

To examine the effect of scan frequency on preventing CHF, the incidence of CHF after MUGA scan intervals of 3 months and 6 months will be described.

Overall survival [ Time Frame: From the date of registration to up to10 years ] [ Designated as safety issue: No ]

Psychometric properties assessed by the PROMIS Fatigue-SF1 measure [ Time Frame: Up to week 22 ] [ Designated as safety issue: No ]

For each of the two instruments, descriptive statistics at each timepoint, including Cronbach's alpha, will be provided. Repeated measures analyses will be used to examine the treatment and time effects on scores. Spearman's correlation coefficient will be used to explore associations between scores on the FACIT Fatigue subscale and scores on the PROMIS Fatigue-SF1.

Scan frequency in preventing CHF [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]

The incidence of CHF after MUGA scan intervals of 3 months and 6 months will be described along with changes in LVEF over these intervals.

Original Secondary Outcome Measures ICMJE

Not Provided

Current Other Outcome Measures ICMJE

Not Provided

Original Other Outcome Measures ICMJE

Not Provided

Descriptive Information

Brief Title ICMJE

Sunitinib Malate or Sorafenib Tosylate in Treating Patients With Kidney Cancer That Was Removed By Surgery

This randomized phase III trial studies sunitinib malate to see how well it works compared to sorafenib tosylate or placebo in treating patients with kidney cancer that has been removed by surgery. Sunitinib malate and sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving sunitinib malate or sorafenib tosylate after surgery may kill any tumor cells that remain after surgery. It is not yet known whether sunitinib malate is more effective than sorafenib tosylate or placebo in treating kidney cancer.

I. To compare overall survival of patients randomized to each of the two regimens with placebo.

II. To further define the toxicity of prolonged administration of sunitinib or sorafenib in this patient population.

III. To prospectively collect tumor and biological specimens to assess their characteristics and associations: novel approaches to assess angiogenesis markers in tissue, blood and urine as predictors of disease-free survival and of therapeutic benefit.

IV. To prospectively collect tumor and biological specimens to assess their characteristics and associations: the frequency of oncogene and tumor suppressor gene mutations as predictors of disease-free survival and therapeutic benefit.

V. To prospectively collect tumor and biological specimens to assess their characteristics and associations: tumor and genetic polymorphisms as predictors of disease-free survival and therapeutic benefit.

VI. To prospectively collect tumor and biological specimens to assess their characteristics and associations: deoxyribonucleic acid (DNA) methylation profiles as predictors of outcome and of therapeutic benefit.

VII. To prospectively collect tumor and biological specimens to assess their characteristics and associations: The relationship of polymorphisms in drug metabolizing enzymes with steady state concentrations of sorafenib and sunitinib in selected patients.

IX. To prospectively assess patient-reported fatigue in order to compare the magnitude and trajectory of fatigue among renal cell carcinoma (RCC) patients randomized to adjuvant sunitinib (Arm A) or sorafenib (Arm B) to placebo (Arm C). (Quality of life objectives) X. To evaluate the Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue-Short Form (SF)1, a newly developed state-of-the-science PROMIS measure for fatigue and to calibrate the PROMIS Fatigue-SF1 with the established, validated FACIT-Fatigue scale. (Quality of life objectives)

No prior anti-cancer therapy for renal cell carcinoma is permitted in either the adjuvant or neoadjuvant setting; this includes metastectomy for renal cell carcinoma, or radiation therapy to the renal bed

Patients must not have other current malignancies, other than basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast; patients with other malignancies are eligible if they have been continuously disease-free for >= 5 years prior to the time of registration

Patients must not have any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism

Patient must not have ongoing ventricular cardiac dysrhythmias of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 grade >= 2; patients with a history of serious ventricular arrhythmia (ventricular tachycardia [VT] or ventricular fibrillation [VF] >= 3 beats in a row) are also excluded; additionally, patients with ongoing atrial fibrillation are not eligible

Patient must not have pre-existing thyroid abnormality with thyroid stimulating hormone that cannot be maintained in the normal range with medication

If female, patient must not be pregnant or breastfeeding; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to pre-registration to rule out pregnancy; if pre-registration occurs prior to surgery, the blood or urine study must be repeated within 2 weeks prior to randomization to rule out pregnancy; (note: should a woman become pregnant while participating in this study, she should inform her treating physician immediately)

Women of child-bearing potential and men must agree to use an accepted and effective method of contraception prior to study entry and for the duration of study participation; should a woman become pregnant while participating in this study, she should inform her treating physician immediately; if a man impregnates a woman while participating in this study, he should inform his treating physician immediately as well

Patients with known human immunodeficiency virus (HIV) are excluded

ELIGIBILITY CRITERIA FOLLOWING RADICAL OR PARTIAL NEPHRECTOMY

The date of randomization must be less than 12 weeks after the date of surgery; patients must have recovered from any surgical related complications

Patients must have histologically or cytologically confirmed renal cell carcinoma. Using 2002 (American Joint Committee on Cancer [AJCC] 6th edition) TNM Staging, patients must be one of the following:

pT1b G3-4 N0 (or pNX where clinically N0) M0

pT2 G (any) N0 (or pNX where clinically N0) M0

pT3 G (any) N0 (or pNX where clinically N0) M0

pT4 G (any) N0 (or pNX where clinically N0) M0 or

T (any) G (any) N+ (fully resected) M0

Patients with microvascular invasion of the renal vein of any grade or stage (as long as M0) are also eligible

Patients must have undergone a full surgical resection (radical nephrectomy or partial nephrectomy) by either open or laparoscopic technique; clinical evidence of lymph node positivity requires removal of all clinically positive nodes; surgeons should designate extent of node dissection; all surgical specimens must have negative margins; patients with positive renal vein margins are eligible unless there is invasion of the renal vein wall at the margin (provided no other margins are positive)

Patients must not have collecting duct carcinomas or medullary carcinomas

Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

Patients must have an absolute baseline left ventricular ejection fraction (LVEF) of >= 50% by multigated acquisition (MUGA) scan within 4 weeks prior to randomization

Patients must have paraffin-embedded tumor specimen available for central core review of tumor histology and other correlative studies; tumor samples will be shipped as specified

Patients must have no evidence of residual or metastatic renal cell cancer as documented on computed tomography (CT) scans of the chest, abdomen, and pelvis, all with oral and intravenous (IV) contrast (magnetic resonance imaging [MRI] scans of the abdomen and pelvis with gadolinium and a non-contrast CT of the chest may be substituted if patient is not able to have CT scans with intravenous contrast); patients unable to tolerate either gadolinium or IV contrast should not participate in this study (limitations to a patient's renal function should be taken into consideration when screening for this study)

Scans must be obtained within 4 weeks of randomization; changes on these scans that are felt to be post surgical must be documented

Patients without reported lymph nodes in the resected surgical specimen and a reported pathologic stage (post-nephrectomy) of pNX MUST undergo a post-operative contrast-enhanced CT scan (or MRI with gadolinium) within 4 weeks of randomization to document that there is no evidence of residual disease